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SH-U-454

✓ Approved

Bayer AG · 小分子 · 小分子

什么是 SH-U-454？

SH-U-454 是一种小分子，由Bayer AG研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

公司Bayer AG
药物类别小分子, 影像药物
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Bayer AG

治疗适应症

SH-U-454 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Cardiac disordersArteriosclerosis coronary artery✓ Approved

相关研究文献

PubMedBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences2026-06-13

[Effect of LncRNA DANCR on the immune microenvironment of glioma cells by regulating the miR-656/BMPR1A axis].

Wang Ouyang O, Zhu Penglei P, Lin Jie J, Wu Hao H

To investigate the effect of long non-coding RNA (LncRNA) differentiation antagonizing non-protein coding RNA (DANCR) on the immune microenvironment of glioma cells by regulating the miR-656/bone morphogenetic protein receptor type 1A (BMPR1A) axis. The expression levels of DANCR, miR-656 and BMPR1A in glioma cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The U87 cells were transfected or co-transfected to form the following groups: sh-DANCR (transfected with sh-DANCR), overexpression (pcDNA 3.1) DANCR (transfected with pcDNA 3.1 DANCR), NC sh (transfected with negative control sh), pcDNA 3.1 (transfected with pcDNA 3.1 vector), sh-DANCR + miR-656 inhibitor (co-transfected with sh-DANCR and miR-656 inhibitor), sh-DANCR + NC inhibitor (co-transfected with sh-DANCR and NC inhibitor), sh-DANCR + pcDNA 3.1 BMPR1A (co-transfected with sh-DANCR and pcDNA 3.1 BMPR1A), and sh-DANCR + pcDNA 3.1 (co-transfected with sh-DANCR and pcDNA 3.1 BMPR1A). The untreated U87 cells were used as the blank group. The proliferation of U87 cells was detected by CCK-8; invasion and migration were detected by Transwell assay; apoptosis was detected by flow cytometry; the expression of DANCR, miR-656, and BMPR1A mRNA in cells was detected by qRT-PCR; the targeting relationship between DANCR and miR-656 was verified by dual-luciferase; and BMPR1A and immune escape factors [programmed death receptor 1 (PD-1) and programmed death-ligand 1 (PD-L1)] were detected by Western blot. The mRNA expressions of DANCR and BMPR1A in U87, A172, LN229 and U251 cells were significantly increased, while the expression of miR-656 was significantly decreased compared with those in NHA cells (P < 0.05). Compared with the blank group and sh-DANCR group, the proliferation rate, invasion, migration number, DANCR, BMPR1A mRNA, BMPR1A, PD-1, PD-L1 expression of U87 cells in the sh-DANCR group were obviously reduced, while the apoptosis rate and miR-656 expression were obviously increased (P < 0.05). Compared with the pcDNA 3.1 group, the proliferation rate, invasion, migration number, DANCR, BMPR1A mRNA, BMPR1A, PD-1, and PD-L1 expression of U87 cells in the pcDNA 3.1 DANCR group were obviously increased, while the apoptosis rate and miR-656 expression were obviously reduced (P < 0.05). Compared with the sh-DANCR +NC inhibitor group, the proliferation rate, invasion, migration number, BMPR1A mRNA, BMPR1A, PD-1, and PD-L1 expression of U87 cells in the sh-DANCR+miR-656 inhibitor group were obviously increased, and the apoptosis rate and miR-656 expression were obviously reduced (P < 0.05), while the expression of DANCR was not obvious (P>0.05). Compared with the sh-DANCR+pcDNA 3.1 group, the proliferation rate, invasion, migration number, BMPR1A mRNA, BMPR1A, PD-1, and PD-L1 expression of U87 cells in the sh-DANCR+pcDNA 3.1 BMPR1A group obviously increased, and the apoptosis rate obviously decreased (P < 0.05), while here was no statistically obvious difference in miR-656 expression and DANCR expression (P>0.05). DANCR and miR-656 had a targeted negative regulatory relationship. LncRNA DANCR improves the immune microenvironment of glioma cells and inhibits the malignant behavior development of cancer cells by regulating the miR-656/BMPR1A axis.

PMID 42287058
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PubMedBMJ open gastroenterology2026-06-13

Safety and effectiveness of the Colovac anastomosis protection device compared with diverting ileostomy after low anterior resection: protocol for an international, multicentre, prospective, non-randomised comparative study (SAFE-3).

Pastier Clément C, Sylla Patricia P, Lee Sang W SW, Spinelli Antonino A et al.

Diverting loop ileostomy (DLI) after low anterior resection for rectal cancer reduces the clinical consequences of anastomotic leakage but is associated with significant morbidity, impaired quality of life and the need for a second operation for stoma closure. Temporary intraluminal bypass devices have been developed to protect the anastomosis while avoiding DLI. However, high-quality prospective data comparing such devices with standard DLI remain limited. This study aims to evaluate the safety and effectiveness of the Colovac device compared with DLI. SafeHeal Studies (SAFE-3), consisting of SafeHeal Standard of Care (Diverting Ileostomy) study (SH-SOC23) and SafeHeal Colovac Anastomosis Protection Device Evaluation Pivotal Study (SAFE-3CV), is an international, multicentre, prospective, non-randomised comparative study comprising two sequential cohorts: SH-SOC23 (standard-of-care diverting ileostomy control) and SAFE-3CV (Colovac anastomosis protection device). A total of 233 patients will be enrolled (SAFE-3CV n=108-120; SH-SOC23 n=132) across 25 centres in 4 countries. The primary endpoints are the rate of major complications at 9 months for safety and stoma avoidance at day 10 for effectiveness. Secondary outcomes include overall postoperative morbidity, stoma-related complications, reoperation rates, length of stay and stoma avoidance. Sample size calculation is based on non-inferiority assumptions. Data will be analysed using intention-to-treat principles, with propensity score adjustment to account for baseline differences between cohorts. Comparative analyses will include logistic regression and sensitivity analyses. The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. An independent safety monitoring committee regularly reviews adverse events and safety data throughout the study. Results will be disseminated through peer-reviewed publications and presentations at international meetings. SH-SOC23: NCT06152276 and SAFE-3CV: NCT07116668.

PMID 42285586
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PubMedNeurotoxicology2026-06-13

Combined exposure to 6PPD and 6PPD-Q induced neurotoxic responses in zebrafish and SH-SY5Y cells: evidence from neurotransmitter disruption, oxidative damage, and apoptosis.

Wang Ziwei Z, Wang Shutao S, Li Wanlun W, Wang Xingyu X et al.

The rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone derivative (6PPD-Q) are coexisting environmental contaminants with documented neurobehavioral effects. However, the neurotoxic consequences arising from their combined exposure remain unclear. In this study, adult zebrafish and SH-SY5Y cells were used to investigate the neurotoxic effects associated with co-exposure to 6PPD and 6PPD-Q. In zebrafish, 100μg/L 6PPD+100μg/L 6PPD-Q increased time spent and distance traveled in the non-reward area of the T-maze after 28 d exposure, accompanied by pathological damage in brain tissue, including reduced neuronal density, decreased Nissl bodies, and apoptosis. 6PPD-Q exacerbated oxidative damage and the decreased levels of neurotransmitters induced by 6PPD. Metabolomics implicated disruptions in neuroactive ligand-receptor interaction and citrate cycle. Transcriptomic analysis further identified dysregulation in oxidative stress, cell death, and nervous system processes related pathways, such as Peroxisome, Axon guidance, and PI3K-Akt pathway. In SH-SY5Y cells, co-exposure reduced cell viability and produced predominantly synergistic effects across concentration combinations tested. 6PPD-Q aggravated mitochondrial damage and enhanced the protein expression levels related to apoptosis induced by 6PPD, including caspase-3 and bax/bcl-2. Moreover, co-exposure inhibited the PI3K-AKT pathway, which might exacerbate neurotransmitter disturbance and apoptosis. The findings enrich the understanding of neurological health risks linked to 6PPD and 6PPD-Q, highlighting the importance of preventive strategies to mitigate the exposure risks.

PMID 42285362
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PubMedScientific reports2026-06-13

Calibration-free physics-informed multi-task residual U-Net for simultaneous denoising and gas pressure retrieval from noisy voigt spectra.

Raheemi Bahambari Alireza A, Khorsandi Alireza A

We present a machine learning framework based on a one-dimensional U-Net (1D U-Net) that simultaneously performs spectral denoising and pressure estimation within a unified architecture. The model is trained on simulated Voigt profiles of the P(21) CO absorption line over pressures ranging from of 1 mbar to 2 bar. To ensure realistic conditions, simulated spectra are superimposed with experimentally captured noise, making them nearly indistinguishable from real experimental scans and forcing the model to recover clean spectra from noisy inputs. Quantitative assessments indicate excellent reconstruction performance, with a Pearson correlation coefficient (PCC) approaching unity, a signal-to-noise ratio (SNR) exceeding 35 dB, and both mean absolute error (MAE) and mean squared error (MSE) remaining close to zero. The model accurately predicts pressures for 200 unseen spectra using only spectral features, bypassing traditional linewidth analysis. At 1.25 bar, the U-Net yields virtually zero error (AE ≈ 0, SE ≈ 0), demonstrating sub-percent deviation and excellent consistency with the simulated reference. Experimental validation on a difference-frequency generation (DFG) spectrometer confirms robust performance, with ≈ 70% of traces reaching a peak SNR (PSNR) above 34 dB. Pressure estimation from ramp-based scans further demonstrates high accuracy, achieving minimal errors at 539.1 mbar (AEP = 0.002, SEP = 4.0 × 10⁻⁶). These findings establish the 1D U-Net as an efficient and reliable alternative to conventional noise-reduction and pressure-estimation techniques, simplifying mid-infrared spectroscopy workflows while ensuring high fidelity and stability.

PMID 42286221
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PubMedBMC nutrition2026-06-13

Association of macronutrient quality at dinner versus breakfast with body composition in adults living in Tehran: results from a cross-sectional study.

Ghaemi Shadi S, Norouziasl Reyhane R, Bafkar Negar N, Ganjeh Bahareh Jabbarzadeh BJ et al.

We aimed to examine the relationship between the quality of macronutrients consumed at dinner versus breakfast and their effects on body composition among Iranian adults. A cross-sectional study was conducted among 450 Iranian adults (aged 20-59). Anthropometric and body composition measures, including BMI, body fat percentage, fat-free mass, muscle mass, and waist-to-hip ratio, were assessed. Dietary data were collected using three 24-hour recalls, categorizing macronutrient quality (carbohydrates, fats, and proteins). ANCOVA was used to compare anthropometric and body composition measures across macronutrient tertiles for dinner versus breakfast. Non-linear associations were analyzed using restricted cubic splines. According to our findings, higher-quality carbohydrate intake at dinner versus breakfast showed a significant inverted U-shaped association with BMI. Conversely, saturated fat intake at dinner versus breakfast increased BMI in a U-shaped relationship, while linearly reducing muscle mass and fat-free mass. Unsaturated fat intake at dinner compared to breakfast showed a U-shaped association with BMI. Moreover, animal protein intake at dinner versus breakfast slightly increased muscle mass and fat-free mass in a reverse U-shaped pattern. However, higher plant protein intake at dinner versus breakfast reduced BMI linearly and decreased fat-free mass and muscle mass. Higher intake of high-quality carbohydrates, unsaturated fats, and plant-based proteins at dinner versus breakfast may improve body composition, while increased consumption of saturated fats and animal proteins at dinner versus breakfast may worsen central adiposity and BMI.

PMID 42286750
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PubMedJournal of physics. Condensed matter : an Institute of Physics journal2026-06-13

Comparing and assessing the thermophysical and structural predictions of an Empirical and a Machine-learning interatomic potentials on liquid (U,Zr).

Canducci Matteo M, Beeler Benjamin B, Bourasseau Emeric E, Malfreyt Patrice P et al.

Liquid uranium-zirconium (U,Zr) mixtures play a crucial role in the context of nuclear accident scenarios, particularly in the early stages of Pressurized-Water Reactor accidents. In this study, we compare the thermophysical and structural predictions of two interatomic potentials for this system, namely a Modified-Embedded Atom Model (MEAM) semi-empirical interatomic potential and a Spectral Neighbor Analysis Potential (SNAP). These models are employed to investigate the relationship between the viscosity, density, and structural properties of liquid (U,Zr) mixtures, and compare their respective predictions. More specifically, the MEAM potential predicts a significant viscosity anomaly at a molar fraction of approximately 70% of Zr. A thorough structural analysis leveraging radial distribution functions and structure factors, Voronoi tessellation, average degree of five-fold local symmetry, and common neighbor analysis supports these findings and attributes them to the formation of an icosahedral short-range order. In contrast, this structural ordering is not observed with the ab initio and SNAP-based computations. We finally analyze those differences and suggest that the semi-empirical MEAM potential may overestimate ordering effects in the liquid phase. These new results can play a role in the refinement of nuclear fuel models, improving the available recommendations for in-vessel corium retention simulations aimed at mitigating severe accident scenarios.

PMID 42285141
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